Synthesis and structural investigation of a series of mannose-containing oligosaccharides using mass spectrometry.

A series of compounds associated with naturally occurring and biologically relevant glycans consisting of α-mannosides were prepared and analyzed using collision-induced dissociation (CID), energy-resolved mass spectrometry (ERMS), and 1H nuclear magnetic resonance spectroscopy. The CID experiments of sodiated species of disaccharides and ERMS experiments revealed that the order of stability of mannosyl linkages was as follows: 6-linked > 4-linked ≧ 2-linked > 3-linked mannosyl residues. Analysis of linear trisaccharides revealed that the order observed in disaccharides could be applied to higher glycans. A branched trisaccharide showed a distinct dissociation pattern with two constituting disaccharide ions. The estimation of the content of this ion mixture was possible using the disaccharide spectra. The hydrolysis of mannose linkages at 3- and 6-positions in the branched trisaccharide revealed that the 3-linkage was cleaved twice as fast as the 6-linkage. It was observed that the solution-phase hydrolysis and gas-phase dissociation have similar energetics.

Late reperfusion (6-24 hours after onset) improves left ventricular function in patients with acute myocardial infarction.

The TAMI-6 trial has demonstrated that coronary reperfusion >6h after onset (ie, late reperfusion) in patients with acute myocardial infarction (AMI) does not improve left ventricular (LV) function during the chronic phase of infarction. However, the low patency rate (only 60%) of the infarct-related artery (IRA) during the chronic phase in the TAMI-6 trial raises a new hypothesis that late reperfusion with a higher patency rate may improve LV function during the chronic phase. Forty-four patients with AMI, who were admitted to hospital 6-24h after the symptom onset and in whom emergency coronary angiography revealed a total occlusion of the IRA, were randomly assigned to either the late reperfusion group (n=22) or the non-reperfusion group (n=22). The initial success rate of reperfusion therapy in the late reperfusion group was 86% and the chronic patency rate of the IRA was 91%. The improvements in ejection fraction and chord shortening in the infarct region from the acute phase to the chronic phase were significantly greater in the late reperfusion group than in the non-reperfusion group. Late reperfusion with a high patency rate of the IRA significantly improves LV global and regional function in patients with AMI.

Is inflammation related to the clinical severity of unstable angina?

The present study determined the white blood cell (WBC) count and the serum C-reactive protein (CRP) level in 27 patients with coronary spastic angina, 16 with Braunwald class IB unstable angina (UA) and 13 with Braunwald class IIIB. The relationship between the clinical presentation of UA and the requirement for emergency percutaneous transluminal coronary angioplasty (PTCA) was examined, and in patients with medically refractory angina, the determining factor among the clinical manifestations of angina was also investigated. In the acute phase, the WBC count and the serum CRP level were significantly higher in patients with Braunwald class IIIB than in those with coronary spastic angina or Braunwald class IB UA (p<0.001). In the Braunwald class IIIB group, a significantly higher rate of patients required emergency PTCA than that of the coronary spastic angina group (p<0.01). Patients with medically refractory angina had a significantly higher WBC count and higher serum CRP level on admission, and the WBC count on admission was independently associated with medically refractory angina by multivariate analysis (p<0.05). Inflammation may play a major pathological role in the rapid development of acute coronary syndrome.

Appropriate indications for the use of a percutaneous cardiopulmonary support system in cases with cardiogenic shock complicating acute myocardial infarction.

Percutaneous cardiopulmonary support (PCPS) is now available for hemodynamic support in patients with cardiogenic shock, but there are no guidelines for its use. The present study determined the appropriate indications for the use of the PCPS in patients with cardiogenic shock complicating acute myocardial infarction (AMI). Sixty-four consecutive patients with cardiogenic shock complicating AMI had hemodynamic support with an intraaortic balloon pump (IABP; n=38) and/or PCPS (n=26). The shock score (0-15) was calculated immediately before starting these support systems to quantify the severity of shock. Multivariate logistic regression analysis determined the clinical factors affecting in-hospital mortality. The relationship between in-hospital prognosis and the shock score was also examined in the 2 groups. The most significant factor related to the in-hospital prognosis was the shock score (p=0.0007; OR 2.16, 95% CI: 1.37-3.39). Another related factor was revascularization; however, this relationship did not reach statistical significance (p=0.069; OR 0.06). Among the 13 cases whose shock score was 4-8 (moderate shock), 5 survived in the PCPS group, but only 1 of 19 patients survived in the IABP group (p<0.05). None of the patients in either group whose shock score was more than 9 survived. The severity of shock is the most reliable independent predictor of in-hospital mortality in patients with cardiogenic shock complicating AMI. Using PCPS in patients with moderate cardiogenic shock may improve their in-hospital survival, but it must be used before the shock becomes severe.

Usefulness of serum troponin T levels on day three or four in predicting survival after acute myocardial infarction.

The appearance of serum troponin T (tn-T) on day 1 after acute myocardial infarction (AMI) strongly depends on coronary reperfusion. In contrast, the kinetics of tn-T release after day 1 after AMI are unaffected by the reperfusion status, and reflect the degradation of myofilaments in irreversibly damaged cells. However, it is not known whether serum tn-T levels after day 1 after AMI can be used to predict the long-term outcome. The purpose of this study was to elucidate the prognostic value of determining the tn-T level on day 3 or 4 after AMI. Serum tn-T levels on day 3 or 4 after AMI were measured in 121 patients (92 men and 29 women, mean age 65 years). Mean follow-up period was 526 days. There were 12 deaths (9 cardiac and 3 noncardiac) during the follow-up period. By Kaplan-Meier analysis, patients with tn-T levels higher than the median level (6.9 ng/ml) had a significantly higher mortality rate than those with submedian levels (p <0.01). By multivariate Cox proportional-hazards regression analysis, the serum tn-T level was an independent predictor of the long-term outcome after AMI (p <0.01). Futhermore, in patients with a first AMI, the serum tn-T level exhibited a significant negative linear correlation with left ventricular ejection fraction assessed 4 weeks after AMI (r = -0.48, p <0.001). Increased serum tn-T levels on day 3 or 4 after AMI are a powerful noninvasive predictor of poor long-term prognosis, reflecting residual left ventricular function after AMI.

Initial experience with nifekalant hydrochloride (MS-551), a novel class III antiarrhythmic agent, in patients with acute extensive infarction and severe ventricular dysfunction.

Nifekalant hydrocholoride, a novel class III antiarrhythmic agent, was used as the treatment in 4 patients with extensive anterior infarction and severe ventricular dysfunction. The malignant ventricular tachyarrhythmia was effectively suppressed at a relatively low dose, without compromising the hemodynamics, indicating that this potent K+ channel blocker has therapeutic potential for acute myocardial infarction.

Esophageal perforation associated with profound shock successfully managed with hemodynamic assistance using percutaneous cardiopulmonary support.

A 51-year-old man was admitted to our hospital with complaints of severe chest pain, nausea, and vomiting. These symptoms had progressed rapidly and he was in shock. It was necessary to make a correct diagnosis as early as possible. However, the hemodynamic condition of the patient deteriorated rapidly before a definitive diagnosis could be established in spite of conventional therapies. Under hemodynamic assistance with percutaneous cardiopulmonary support (PCPS), a final diagnosis of esophageal perforation was made by esophagography. Our report illustrates a new application of PCPS for highly selected cases of noncardiogenic shock as a "bridge" until an accurate diagnosis is made and a specific treatment is applied.

Dexamethasone-induced cardiogenic shock rescued by percutaneous cardiopulmonary support (PCPS) in a patient with pheochromocytoma.

A 52-year-old man with pheochromocytoma had cardiogenic shock and was rescued using a percutaneous cardio pulmonary supporting system. After recovery, diagnostic tests including metaiodobenzylguanidine scintigraphy and computed tomography, revealed the pheochromocytoma which was confirmed by histology. It was postulated that the acute episode was induced by intra-joint dexamethasone, which increased the production of epinephrine and augmented the sensitivity of cardiomyocytes for catecholamine, thereby inducing the cardiomyopathy.

Circulating hepatocyte growth factor as a marker of thrombus formation in unstable angina pectoris.

A new enzyme-linked immunosorbent assay can detect 10 pg/ml of human hepatocyte growth factor (HGF). Circulating HGF was significantly higher in patients with unstable angina (296+/-184 pg/ml, mean+/-SD, n=36) than in healthy volunteers (201+/-64 pg/ml, n=250, p<0.0001). Individual concentrations exceeded the mean control value +2 SD (329 pg/ml) in 12 of the 36 (33%) patients with unstable angina. The present study indicates that this new, sensitive HGF assay can successfully detect thrombosis in patients with unstable angina.

Abnormal glucose tolerance, not small vessel diameter, is a determinant of long-term prognosis in patients treated with balloon coronary angioplasty.

AIMS: We sought to find out what factors are important for long-term prognosis, the small vessel itself or abnormal glucose tolerance, in patients treated with coronary angioplasty. BACKGROUND: Patients with coronary artery disease with diabetes mellitus often show diffuse and small coronary artery narrowing. Impaired glucose tolerance has also been reported to be a risk factor for cardiovascular disease. METHODS: Among 584 patients who underwent first elective balloon coronary angioplasty, diabetes mellitus and impaired glucose tolerance were present in 197 patients. Large and small vessels were defined by reference vessel diameter before coronary angioplasty as either larger or smaller than 2.5 mm. Patients were categorized into the following four groups: 175 patients with normal glucose tolerance and reference diameter <2.5 mm (group SN), 212 patients with normal glucose tolerance and reference diameter greater than or = 2.5 mm (group LN), 101 patients with abnormal glucose tolerance and reference diameter <2.5 mm (group SD), and 96 patients with abnormal glucose tolerance and reference diameter greater than or = 2.5 mm (Group LD). The cardiac events were compared for a period of 8 years after coronary angioplasty among the four groups. RESULTS: There was no difference in the percentage diameter stenosis immediately after coronary angioplasty among the four groups. However, group SD showed unfavourable prognosis despite similar minimal lumen diameter after coronary angioplasty compared with group SN. Event-free survival curve of group LD showed a sudden drop approximately 5 years after the coronary angioplasty. In multivariate analysis, the cardiac events were associated with the presence or absence of abnormal glucose tolerance. Furthermore, patients with bad glycaemic control (HbA1c>6.0%) at index coronary angioplasty showed worse event free survival than those with good glycaemic control. CONCLUSIONS: An important determinant for long-term prognosis after coronary angioplasty is a presence of abnormal glucose tolerance per se and not small vessel diameter.

[Risk factors and physical activity levels at the onset of acute myocardial infarction in young men].

OBJECTIVES: The pathogenesis and triggering factors of acute myocardial infarction in young men remain unknown. To clarify the pathogenesis of acute myocardial infarction in young Japanese men, we compared the clinical features of patients with acute myocardial infarction in 2 age groups in Japan. METHODS: There were 37 male patients aged < 40 years (Young group; mean age 36 +/- 4 years, range 23-39 years) among 2,879 patients with acute myocardial infarction admitted to the coronary care unit of the National Cardiovascular Center, Japan, from 1977 through 1996. The clinical features of this group were compared with those of 110 consecutive male patients with acute myocardial infarction aged > or = 65 years (Old group; mean age 72 +/- 6 years, range 65-96 years) admitted in 1993-1994. Demographic features, physical activity levels at or within 2 hours before the onset of acute myocardial infarction, and coronary angiographic findings were analyzed. RESULTS: Compared with the Old group, the Young group had lower incidences of hypertension (p < 0.01) and diabetes mellitus (p < 0.01), a higher incidence of smoking (p < 0.01), higher levels of total cholesterol (p < 0.05) and body mass index (p < 0.05), and a lower level of high-density lipopotein (HDL)-cholesterol (p < 0.01). Also, the Young group had a higher prevalence of 0-1 vessel disease than the Old group (72% vs 35%, p < 0.01). The physical activity level was significantly higher in the Young group than in the Old group (2.6 +/- 2.2 vs 1.8 +/- 1.1 METs, p < 0.01). Furthermore, patients with multivessel disease in the Young group had a higher incidence of hypertension, a higher level of total cholesterol and a lower level of HDL-cholesterol (all p < 0.05), whereas those with 0-1 vessel disease had a higher incidence of heavy smoking (73% vs 50%, p = 0.1) and a tendency to higher physical activity level at the onset (2.7 +/- 2.2 vs 2.4 +/- 2.3, NS). CONCLUSIONS: Young male patients with acute myocardial infarction may be characterized by 2 distinctive patterns: one associated with smoking and a higher physical activity level at the onset of acute myocardial infarction with 0-1 vessel disease and the other with hypertension and hypercholesterolemia with multivessel disease.

Refractory coronary spasm relieved by intracoronary administration of nicorandil.

Two patients in whom coronary spasm was refractory to intracoronary injection of nitroglycerin were relieved by intracoronary administration of nicorandil (a nitrate and potassium channel opener) during catheterization. These findings suggest that nicorandil may prove useful as an additional therapeutic agent.

A randomised controlled trial of Prostar Plus for haemostasis in patients after coronary angioplasty.

OBJECTIVES: to clarify the efficacy and safety of Prostar Plus, a new percutaneous vascular surgical device (PVS) for vascular haemostasis. DESIGN: prospective randomised controlled trial. METHODS: a consecutive series of 60 patients were randomised to either PVS (n =30) or conventional manual compression ( n =30) following coronary angioplasty or stenting with femoral access using an 8-F sheath. RESULTS: PVS significantly shortened the time to haemostasis (10 s.d. 3 vs. 27 s.d. 9 min, p <0.001), ambulation (2.2 s.d. 0.9 vs. 11.0 s.d. 1.4 h, p <0.001), and discharge (2.2 s.d. 0.4 vs. 3.1 s.d. 0.7 days, p <0.01), compared with the manual compression group with no major complications. PVS also increased patient comfort assessed by using a visual-analogue scale method. Although these clinical benefits reduced the hospital cost ($1301 s. d. 248 vs. 1613 s.d. 460, p <0.05), the cost of the PVS device (approximately $350) cancelled the cost-saving benefit. CONCLUSIONS: this randomised study indicates that Prostar Plus is safe, more effective and comfortable than conventional manual compression.

Percutaneous transluminal coronary angioplasty of chronic total occlusions. Determinants of primary success and long-term clinical outcome.

This study was conducted to assess the determinants of the procedural success and long-term clinical benefits of percutaneous transluminal balloon angioplasty (PTCA) of chronic total occlusion (CTO) in recent years. Two hundred and twenty-six consecutive patients who underwent PTCA of CTO were divided into two groups according to the procedural success (n = 134) or failure (n = 92). Both groups were analyzed in terms of the initial success, predictors of procedural failure, and clinical outcome. The procedural success rate was noted to have improved to more than 70% since 1995. A multiple logistic regression analysis revealed that the presence of calcification, the length of the occlusion and the presence of multivessel disease were independent predictors of procedural failure. Cardiac death and the need for coronary surgery were significantly less frequent in patients with procedural success than in those with procedural failure. In properly selected cases, the success rate of PTCA of CTO is acceptable. Long-term clinical benefit is suggested by the high rate of freedom from coronary surgery and the low cardiac death rate in the patients who underwent successful revascularization.

Pulsatile gonadotropin-releasing hormone (GnRH) secretion is an inherent function of GnRH neurons, as revealed by the culture of medial olfactory placode obtained from embryonic rats.

To determine whether gonadotropin-releasing hormone (GnRH) neurons in culture without the hypothalamus secrete GnRH in a pulsatile fashion, the nasal placode (NAP) was obtained at day 13.5 of gestation and cultured by a roller tube method. If the GnRH release occurs in a pulsatile fashion, it can be said that the pulse generator of GnRH exists inherently in each cell or community of cells in the culture. The concentration of GnRH in the NAP culture medium collected at 8-min intervals for 160 min after 2- to 4-week cultures showed that GnRH release occurred in a pulsatile fashion with a mean interpulse interval of 29.8 +/- 2.3 min (n = 9). When the NAP was cultured with tissues of the forebrain vesicle (n = 3) or the hypothalamus (n = 4), GnRH was also released in a pulsatile fashion with similar intervals (27.3 +/- 1.0 min for the NAP+forebrain vesicle culture and 36.0 +/- 6.3 min for the NAP+hypothalamus culture) as those in cultures without brain tissues. It is concluded that pulsatile GnRH release is an inherent function of GnRH neurons.

Is preinfarction angina related to the presence or absence of coronary plaque rupture?

OBJECTIVE: To analyse the prodrome of acute myocardial infarction in relation to the plaque morphology underlying the infarct. DESIGN: A retrospective investigation of the relation between rupture and erosion of coronary atheromatous plaques and the clinical characteristics of acute myocardial infarction. The coronary arteries of 100 patients who died from acute myocardial infarction were cut transversely at 3 mm intervals. Segments with a stenosis were examined microscopically at 5 micrometer intervals. The clinical features of the infarction were obtained from the medical records. RESULTS: A deep intimal rupture was encountered in 81 plaques, whereas 19 had superficial erosions only. There were no differences in the location of infarction, the incidence of hypertension, diabetes mellitus, or hyperlipidaemia, diameter stenosis of the infarcted related artery, Killip class, Forrester's haemodynamic subset, or peak creatine kinase between plaque rupture and plaque erosion groups. The presence of plaque rupture was associated with significantly greater incidences of leucocytosis, current smoking, and sudden or unstable onset of acute coronary syndrome. In patients with unstable preinfarction angina, new onset rest angina rather than worsening angina tended to develop more often in the plaque rupture group than in the plaque erosion group (p = 0.08). CONCLUSIONS: Plaque rupture causes the sudden onset of acute myocardial infarction or unstable preinfarction angina, which may be aggravated by smoking and inflammation.

Morphology of vulnerable coronary plaque: insights from follow-up of patients examined by intravascular ultrasound before an acute coronary syndrome.

OBJECTIVES: To determine the morphologic features of coronary plaques associated with acute coronary syndrome, we prospectively followed patients with atherosclerotic disease identified by intravascular ultrasound (IVUS). BACKGROUND: Although clinical evaluation of the vulnerable atherosclerotic plaque is important, few data exist regarding the morphology of the vulnerable plaque in clinical settings. METHODS: We examined 114 coronary sites without significant stenosis by angiography (<50% diameter stenosis) in 106 patients. All the sites exhibited atherosclerotic lesions by IVUS. These lesions consisted of 22 concentric and 92 eccentric plaques with a percent plaque area averaging 59 +/- 12%. RESULTS: During the follow-up period of 21.8 +/- 6.4 months (range 1 to 24), 12 patients had an acute coronary event at a previously examined coronary site at an average of 4.0 +/- 3.4 months after the initial IVUS study. All the preexisting plaques related to the acute events exhibited an eccentric pattern and the mean percent plaque area was 67 +/- 9%, which was greater than plaque area in the other 90 patients without acute events (57 +/- 12%, p < 0.05). There was no statistically significant difference in lumen area between two patient groups (6.7 +/- 3.0 vs. 7.5 +/- 3.7 mm2). Among 12 coronary sites with an acute occlusion, 10 sites contained the echolucent zones, eight of these shallow and two deep, likely representing a lipid-rich core. In 90 sites without acute events, an echolucent zone in the shallow portion was seen at only four sites (p < 0.05). CONCLUSIONS: Large eccentric plaque containing an echolucent zone by IVUS can be at increased risk for instability even though the lumen area is preserved at the time of initial study. Compensatory enlargement of vessel wall due to remodeling may contribute to the relatively small degree of stenosis by angiography.

The olfactory origin of luteinizing hormone-releasing hormone (LHRH) neurons. A new era in reproduction physiology.

This paper reviews those studies which conceived the concept that the brain LHRH-synthesizing neurons originate in the nasal placode. LHRH isolated from mammalian hypothalamus in 1971 was first shown immunohistochemically two years later in the hypothalamic neurons which project processes to the median eminence, to release it into the portal capillaries in the guinea pig. At an early stage of development, the LHRH cells were found in the nasal placode but not in the hypothalamus as shown in in vivo and in vitro developmental studies. The cells arising in the brain were delayed. This discrepancy was solved in 1989-1990 by findings that the cells derived in the placode at an early stage left the site and migrated to the forebrain vesicles along the placode-derived terminal and vomeronasal nerve fibers, both of which were found to express immunoreactive cell adhesion molecules. The neurons, after reaching the surface of the forebrain vesicles, entered into the brain by the guidance of the cell adhesion molecule-positive fibers, and came to be distributed not only in the hypothalamus but also in the telencephalon cortex, midbrain, limbic brain, and main and accessory olfactory bulbs. The attention to these heterogeneties led to discussion of the possible neurobiological significance of this peculiar peripheral neurogenesis from an evolutionary viewpoint.

Influence of calcium antagonists on long-term survival of patients treated with coronary angioplasty.

A meta-analysis reported that nifedipine increased mortality dose-dependently in patients with coronary artery disease. However, there have been few studies (specifically in Asians) on the long-term prognosis of patients treated with calcium antagonists after successful coronary angioplasty (PTCA). The subjects consisted of 583 consecutive patients (461 males, aged 59 +/- 10), who underwent successful elective PTCA between 1985 and 1990. First, they were divided into two groups; the calcium antagonist (+) group (n = 560) and the calcium antagonist (-) group (n = 23), and were evaluated in terms of total survival and cardiac events. Second, the calcium antagonist (+) group was further divided into 4 groups according to calcium antagonist type, i.e., short-acting nifedipine group (n = 156), long-acting nifedipine group (n = 203), diltiazem group (n = 184) and the other group (n = 17), and these groups were evaluated in the same way. The primary end-point was set as death from any cause. Secondary end-points were any cardiac events, including non-fatal acute myocardial infarction, coronary artery bypass surgery and repeat PTCA. The mean follow-up period was 4.5 +/- 1.8 years. A multivariate analysis was performed with the Cox proportional-hazard model. The Kaplan-Meier analysis showed that the calcium antagonist (-) group had significantly worse prognoses than the calcium antagonist (+) group (p < 0.05), and that there was no significant difference among the prognoses of the four calcium antagonists groups. The multivariate analysis revealed that the use of a calcium antagonist was one of the independent factors positively contributing to the prognosis. The use of any type of calcium antagonist did not increase mortality in patients who underwent successful elective PTCA, rather, it contributed to a favorable outcome.